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Chemical Structure| 1165936-03-7

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2-(2-Fluoro-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

CAS No.: 1165936-03-7

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Cat. No.: A753232 Purity: 97%

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Product Details of [ 1165936-03-7 ]

CAS No. :1165936-03-7
Formula : C13H18BFO2
M.W : 236.09
SMILES Code : CC1(C)C(C)(C)OB(C2=CC=C(C)C=C2F)O1
MDL No. :MFCD18779806
InChI Key :MKWDECBHRFNFGY-UHFFFAOYSA-N
Pubchem ID :69672435

Safety of [ 1165936-03-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Application In Synthesis [ 1165936-03-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1165936-03-7 ]

[ 1165936-03-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 1165936-03-7 ]
  • [ 146014-66-6 ]
  • [ 668473-65-2 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; at 80℃; for 16h; EXAMPLE 6 Method F Methyl 4'-[({3-[(cyanoacetyl)amino]-4-methylpyridin-2-yl}amino)methyl]-2',3-difluoro-1,1'-biphenyl-2-carboxylate [0212] [CHEMMOL-00020] [0213] To a stirred solution of 1-bromo-2-fluoro-4-methylbenzene (0.945 g, 5 mmol) in DMF (10 mL) in a sealed tube, bis(pinacolato)diboron (2.29 g, 9 mmol), dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.146 g, 0.2 mmol), and potassium acetate (1.47 g, 15 mmol) were added at room temperature. The resulting mixture was heated at 80 C. for 16 hours to provide 2-(2-fluoro-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, and the solution was cooled to room temperature for the next step without any workup. [0214] To the above solution, <strong>[146014-66-6]methyl 2-fluoro-6-iodobenzoate</strong> (1.40 g, 5 mmol), dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.10 g, 0.15 mmol), and sodium carbonate solution (2 M, 12.5 mL, 25 mmol) were added. The resulting mixture was heated at 80 C. for 16 hours. After cooling to room temperature, the mixture was partitioned between water and diethyl ether. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 10% ethyl acetate in hexanes to provide methyl 2',3-difluoro-4'-methyl-1,1'-biphenyl-2-carboxylate as a yellow oil with a mass ion of ion (ES+) of 263.0 for M+H+. [0215] A mixture of the carboxylate (0.90 g, 3.43 mmol), N-bromo-succinimide (0.672 g, 3.78 mmol), and 2,2'-azobisisobutyronitrile (0.0169, 0.10 mmol) was suspended in 50 mL carbon tetrachloride, and heated to reflux for 5 hours. The reaction mixture was filtered to remove the residue. The resulting filtrate was concentrated under vacuum, and then partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 10% ethyl acetate in hexanes to afford methyl 4'-(bromomethyl)-2',3-difluoro-1,1'-biphenyl-2-carboxylate as a brown oil with a mass ion of ion (ES+) of 341 for M+H+. [0216] To a stirred solution of 2-amino-4-methyl-3-nitropyridine (0.306 g, 2 mmol) in DMF (2 mL) at 0 C., sodium hydride (60% dispersion in mineral oil, 0.040 g, 1 mmol) was added, and stirred at 0 C. for 20 minutes. To the resulting mixture, methyl 4'-(bromomethyl)-2',3-difluoro-1,1'-biphenyl-2-carboxylate (0.341 g, 1 mmol) was added, and stirring continued at 0 C. for another 30 minutes. The reaction was quenched by the addition of saturated ammonium chloride (5 mL), and partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with 20% ethyl acetate in hexanes to provide methyl 2',3-difluoro-4'-[(4-methyl-3-nitropyridin-2-yl)amino]-methyl}-1,1'-biphenyl-2-carboxylate as a yellow oil with a mass ion of ion (ES+) of 414 for M+H+. [0217] To a stirred solution of the above product (0.11 g, 0.266 mmol) in methanol (2 mL), tin(II) chloride dihydrate (0.24 g, 1.06 mmol) was added and heated in a sealed tube at 70 C. for 2 hours. The resulting solution was concentrated under vacuum. The residue was dissolved in ethyl acetate (20 mL), and 10% aq. sodium carbonate solution was added with vigorous stirring until pH=10. The white suspension was filtered through a pad of Celite, and the filtrate was partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 55% ethyl acetate in hexanes to provide methyl 4'-[(3-amino-4-methylpyridin-2-yl)amino]methyl}-2',3-difluoro-1,1'-biphenyl-2-carboxylate as a yellow solid. [0218] To a solution of the above carboxylate (0.038 g, 0.10 mmol) in DMF (1 mL), cyanoacetic acid (0.026 g, 0.30 mmol), 1-ethyl-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.038 g 0.20 mmol), 1-hydroxy-7-azabenzotriazole (0.0136 g, 0.10 mmol) were added, and N,N-diisopropylethylamine was added until pH=10. The resulting solution was stirred at room temperature for 20 hours, and partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 60% ethyl acetate in hexanes. The appropriate fractions were concentrated under vacuum, and the residue was dissolved in 60 mL of 50% acetonitrile in hydrochloric acid (2 mL conc. hydrochloric acid in 4 L water). Lyophilization of the resulting solution afforded the HCl salt of the title compound as a white solid that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 451 for M+H+: 1H NMR (400 MHz, DMSO) 69.98 (br s, 1H), 7.81 (d, J=6.12 H...
 

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